1021 Samelisant: Clinician and Patient Global Impression from a Double-Blind, Phase-2 Study in Patients with Narcolepsy

Abstract Introduction Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor (H3R) inverse agonist. Samelisant exhibited desired pharmacokinetic properties in rodents and healthy human volunteers. Preclinical studies in orexin knockout mice demonstrated wake promoting and anticataplectic effects of samelisant. To confirm the preclinical findings, Samelisant was evaluated as monotherapy for the treatment of excessive daytime sleepiness (EDS) in patients with narcolepsy with or without cataplexy. The primary endpoint was changes in the Epworth Sleepiness Scale (ESS) scores. Clinician and Patient Global Impression for EDS were assessed as secondary and exploratory endpoints. Methods Two doses of samelisant (2 and 4 mg) were evaluated as a monotherapy in a Phase-2 study for the treatment of EDS in subjects with narcolepsy (ClinicalTrials.gov Identifier: NCT04072380). Subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an ESS score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of 12 min were recruited in the study. A total of 190 subjects were randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio and received either placebo or samelisant once daily for 2 weeks. The primary efficacy endpoint was the change in ESS score from baseline to week 2. Clinical Global Impression – Severity (CGI-S) was a secondary endpoint, whereas change in Patient Global Impression – Change (PGI-C) and Clinical Global Impression of Change (CGI-C) scores related to EDS were exploratory endpoints. Results At the end of the double-blind period, the samelisant treated groups demonstrated clinically and statistically significant improvements in CGI-S (p 0.01), PGI-C (p 0.001) and CGI-C (p 0.0001) with regards to EDS. The proportion of patients reporting improvement in EDS was significantly higher in the samelisant treatment arms compared to placebo arm. Conclusion Treatment with samelisant as monotherapy resulted in significant improvement in excessive day time sleepiness as assessed by both clinicians and patients. These outcomes support the efficacy of samelisant observed in the primary endpoint, ESS, in patients with narcolepsy with or without cataplexy. Support (if any)